The Effect of Interventions to Prevent Type 2 Diabetes on the Development of Diabetic Retinopathy: The DPP/DPPOS Experience
Authors: Neil H. White, Qing Pan, William C. Knowler, Emily B. Schroeder, Dana Dabelea, Emily Y. Chew, Barbara Blodi, Ronald B. Goldberg, Xavier Pi-Sunyer, Christine Darwin, Mathias Schlögl, David M. Nathan, Barry J. Goldstein, Kevin Furlong, Kellie A. Smith, Jewel Mendoza, Wendi Wildman, Marsha Simmons, Genine Jensen, Renee Liberoni, John Spandorfer, Constance Pepe, Richard P. Donahue, Ronald B. Goldberg, Ronald Prineas, Patricia Rowe, Anna Giannella, Jeanette Calles, Juliet Sanguily, Paul Cassanova-Romero, Sumaya Castillo-Florez, Hermes J. Florez, Rajesh Garg, Lascelles Kirby, Olga Lara, Carmen Larreal, Valerie McLymont, Jadell Mendez, Arlette Perry, Patrice Saab, Bertha Veciana, Steven M. Haffner, Helen P. Hazuda, Maria G. Montez, Juan Isaac, Kathy Hattaway, Carlos Lorenzo, Arlene Martinez, Monica Salazar, Tatiana Walker, Richard F. Hamman, Dana Dabelea, Patricia V. Nash, Sheila C. Steinke, Lisa Testaverde, Jennifer Truong, Denise R. Anderson, Larry B. Ballonoff, Alexis Bouffard, Rebecca S. Boxer, Brian Bucca, B. Ned Calonge, Lynne Delve, Martha Farago, James O. Hill, Shelley R. Hoyer, Tonya Jenkins, Bonnie T. Jortberg, Dione Lenz, Marsha Miller, Thomas Nilan, Leigh Perreault, David W. Price, Judith G. Regensteiner, Emily B. Schroeder, Helen Seagle, Carissa M. Smith, Brent VanDorsten, Edward S. Horton, Medha Munshi, Kathleen E. Lawton, Catherine S. Poirier, Kati Swift, Sharon D. Jackson, Ronald A. Arky, Marybeth Bryant, Jacqueline P. Burke, Enrique Caballero, Karen M. Callaphan, Barbara Fargnoli, Therese Franklin, Om P. Ganda, Ashley Guidi, Mathew Guido, Alan M. Jacobsen, Lyn M. Kula, Margaret Kocal, Lori Lambert, Kathleen E. Lawton, Sarah Ledbury, Maureen A. Malloy, Roeland J.W. Middelbeek, Maryanne Nicosia, Cathryn F. Oldmixon, Jocelyn Pan, Marizel Quitingon, Riley Rainville, Stacy Rubtchinsky, Ellen W. Seely, Jessica Sansoucy, Dana Schweizer, Donald Simonson, Fannie Smith, Caren G. Solomon, Jeanne Spellman, James Warram, Steven E. Kahn, Brenda K. Montgomery, Basma Fattaleh, Celeste Colegrove, Wilfred Fujimoto, Robert H. Knopp, Edward W. Lipkin, Michelle Marr, Ivy Morgan-Taggart, Anne Murillo, Kayla O’Neal, Dace Trence, Lonnese Taylor, April Thomas, Elaine C. Tsai, Abbas E. Kitabchi, Samuel Dagogo-Jack, Mary E. Murphy, Laura Taylor, Jennifer Dolgoff, Ethel Faye Hampton, William B. Applegate, Michael Bryer-Ash, Debra Clark, Sandra L. Frieson, Uzoma Ibebuogu, Raed Imseis, Helen Lambeth, Lynne C. Lichtermann, Hooman Oktaei, Harriet Ricks, Lily M.K. Rutledge, Amy R. Sherman, Clara M. Smith, Judith E. Soberman, Beverly Williamsleaves, Avnisha Patel, Ebenezer A. Nyenwe, Boyd E. Metzger, Mark E. Molitch, Amisha Wallia, Mariana K. Johnson, Sarah VanderMolen, Daphne T. Adelman, Catherine Behrends, Michelle Cook, Marian Fitzgibbon, Mimi M. Giles, Monica Hartmuller, Cheryl K.H. Johnson, Diane Larsen, Anne Lowe, Megan Lyman, David McPherson, Samsam C. Penn, Thomas Pitts, Renee Reinhart, Susan Roston, Pamela A. Schinleber, David M. Nathan, Charles McKitrick, Heather Turgeon, Mary Larkin, Marielle Mugford, Nopporn Thangthaeng, Fernelle Leander, Kathy Abbott, Ellen Anderson, Laurie Bissett, Kristy Bondi, Enrico Cagliero, Jose C. Florez, Linda Delahanty, Valerie Goldman, Elaine Grassa, Lindsey Gurry, Kali D’Anna, Fernelle Leandre, Peter Lou, Alexandra Poulos, Elyse Raymond, Valerie Ripley, Christine Stevens, Beverly Tseng, Jerrold M. Olefsky, Elizabeth Barrettonnor, Sunder Mudaliar, Maria Rosario Araneta, Mary Lou Carrion-Petersen, Karen Vejvoda, Sarah Bassiouni, Madeline Beltran, Lauren N. Claravall, Jonalle M. Dowden, Steven V. Edelman, Pranav Garimella, Robert R. Henry, Javiva Horne, Marycie Lamkin, Simona Szerdi Janesch, Diana Leos, William Polonsky, Rosa Ruiz, Jean Smith, Jennifer Torio-Hurley, F. Xavier Pi-Sunyer, Blandine Laferrere, Jane E. Lee, Susan Hagamen, Kim Kelly-Dinham, David B. Allison, Nnenna Agharanya, Nancy J. Aronoff, Maria Baldo, Jill P. Crandall, Sandra T. Foo, Jose A. Luchsinger, Carmen Pal, Kathy Parkes, Mary Beth Pena, Julie Roman, Ellen S. Rooney, Gretchen E.H. VanWye, Kristine A. Viscovich, Melvin J. Prince, David G. Marrero, Kieren J. Mather, Mary De Groot, Susie M. Kelly, Marcia A. Jackson, Gina McAtee, Paula Putenney, Ronald T. Ackermann, Carolyn M. Cantrell, Yolanda F. Dotson, Edwin S. Fineberg, Megan Fultz, John C. Guare, Angela Hadden, James M. Ignaut, Marion S. Kirkman, Erin O’Kelly Phillips, Kisha L. Pinner, Beverly D. Porter, Paris J. Roach, Nancy D. Rowland, Madelyn L. Wheeler, Robert E. Ratner, Vanita Aroda, Michelle Magee, Gretchen Youssef, Sue Shapiro, Natalie Andon, Catherine Bavido-Arrage, Geraldine Boggs, Marjorie Bronsord, Ernestine Brown, Holly Love Burkott, Wayman W. Cheatham, Susan Cola, Cindy Evans, Peggy Gibbs, Tracy Kellum, Lilia Leon, Milvia Lagarda, Claresa Levatan, Milajurine Lindsay, Asha K. Nair, Jean Park, Maureen Passaro, Angela Silverman, Gabriel Uwaifo, Debra Wells-Thayer, Renee Wiggins, Mohammed F. Saad, Karol Watson, Maria Budget, Sujata Jinagouda, Medhat Botrous, Anthony Sosa, Sameh Tadros, Khan Akbar, Claudia Conzues, Perpetua Magpuri, Kathy Ngo, Amer Rassam, Debra Waters, Kathy Xapthalamous, Julio V. Santiago, Samuel Dagogo-Jack, Neil H. White, Angela L. Brown, Ana Santiago, Samia Das, Prajakta Khare-Ranade, Tamara Stich, Edwin Fisher, Emma Hurt, Jackie Jones, Tracy Jones, Michelle Kerr, Sherri McCowan, Lucy Ryder, Cormarie Wernimont, Christopher D. Saudek, Sherita Hill Golden, Vanessa Bradley, Emily Sullivan, Tracy Whittington, Caroline Abbas, Adrienne Allen, Frederick L. Brancati, Sharon Cappelli, Jeanne M. Clark, Jeanne B. Charleston, Janice Freel, Katherine Horak, Alicia Greene, Dawn Jiggetts, Delois Johnson, Hope Joseph, Rita Kalyani, Kimberly Loman, Nestoras Mathioudakis, Nisa Maruthur, Henry Mosley, John Reusing, Richard R. Rubin, Alafia Samuels, Thomas Shields, Shawne Stephens, Kerry J. Stewart, LeeLana Thomas, Evonne Utsey, Paula Williamson, David S. Schade, Karwyn S. Adams, Carolyn Johannes, Claire Hemphill, Penny Hyde, Janene L. Canady, Leslie F. Atler, Patrick J. Boyle, Mark R. Burge, Lisa Chai, Kathleen Colleran, Ateka Fondino, Ysela Gonzales, Doris A. Hernandez-McGinnis, Patricia Katz, Carolyn King, Julia Middendorf, Amer Rassam, Sofya Rubinchik, Willette Senter, Debra Waters, Harry Shamoon, Jill Crandall, Janet O. Brown, Gilda Trandafirescu, Danielle Powell, Elsie Adorno, Liane Cox, Helena Duffy, Samuel Engel, Allison Friedler, Angela Goldstein, Crystal J. Howardentury, Jennifer Lukin, Stacey Kloiber, Nadege Longchamp, Helen Martinez, Dorothy Pompi, Jonathan Scheindlin, Norica Tomuta, Elissa Violino, Elizabeth A. Walker, Judith Wylie-Rosett, Elise Zimmerman, Joel Zonszein, Rena R. Wing, Trevor Orchard, Elizabeth Venditti, Gaye Koenning, M. Kaye Kramer, Marie Smith, Susan Jeffries, Valarie Weinzierl, Susan Barr, Catherine Benchoff, Miriam Boraz, Lisa Clifford, Rebecca Culyba, Marlene Frazier, Ryan Gilligan, Stephanie Guimond, Susan Harrier, Louann Harris, Andrea Kriska, Qurashia Manjoo, Monica Mullen, Alicia Noel, Amy Otto, Jessica Pettigrew, Bonny Rockette-Wagner, Debra Rubinstein, Linda Semler, Cheryl F. Smith, Katherine V. Williams, Tara Wilson, Richard F. Arakaki, Marjorie K. Mau, Renee W. Latimer, Mae K. Isonaga, Narleen K. Baker-Ladao, Ralph Bow, Nina E. Bermudez, Lorna Dias, Jillian Inouye, John S. Melish, Kathy Mikami, Pharis Mohideen, Sharon K. Odom, Raynette U. Perry, Robin E. Yamamoto, William C. Knowler, Robert L. Hanson, Vallabh Shah, Mary A. Hoskin, Carol A. Percy, Norman Cooeyate, Camille Natewa, Charlotte Dodge, Alvera Enote, Harelda Anderson, Kelly J. Acton, Vickie L. Andre, Rosalyn Barber, Shandiin Begay, Peter H. Bennett, Mary Beth Benson, Evelyn C. Bird, Brenda A. Broussard, Brian C. Bucca, Marcella Chavez, Sherron Cook, Jeff Curtis, Tara Dacawyma, Matthew S. Doughty, Roberta Duncan, Cyndy Edgerton, Jacqueline M. Ghahate, Justin Glass, Martia Glass, Dorothy Gohdes, Wendy Grant, Ellie Horse, Louise E. Ingraham, Merry Jackson, Priscilla Jay, Roylen S. Kaskalla, Karen Kavena, David Kessler, Kathleen M. Kobus, Jonathan Krakoff, Jason Kurland, Catherine Manus, Cherie McCabe, Sara Michaels, Tina Morgan, Yolanda Nashboo, Julie A. Nelson, Steven Poirier, Evette Polczynski, Christopher Piromalli, Mike Reidy, Jeanine Roumain, Debra Rowse, Robert J. Roy, Sandra Sangster, Janet Sewenemewa, Miranda Smart, Chelsea Spencer, Darryl Tonemah, Rachel Williams, Charlton Wilson, Michelle Yazzie, Raymond Bain, Sarah Fowler, Michael D. Larsen, Kathleen Jablonski, Marinella Temprosa, Tina Brenneman, Sharon L. Edelstein, Solome Abebe, Julie Bamdad, Melanie Barkalow, Joel Bethepu, Tsedenia Bezabeh, Anna Bowers, Nicole Butler, Jackie Callaghan, Caitlin E. Carter, Costas Christophi, Gregory M. Dwyer, Mary Foulkes, Yuping Gao, Robert Gooding, Adrienne Gottlieb, Kristina L. Grimes, Nisha Grover-Fairchild, Lori Haffner, Heather Hoffman, Steve Jones, Tara L. Jones, Richard Katz, Preethy Kolinjivadi, John M. Lachin, Yong Ma, Pamela Mucik, Robert Orlosky, Qing Pan, Susan Reamer, James Rochon, Alla Sapozhnikova, Hanna Sherif, Charlotte Stimpson, Ashley Hogan Tjaden, Fredricka Walker-Murray, Elizabeth M. Venditti, Andrea M. Kriska, Linda Semler, Valerie Weinzierl, Santica Marcovina, F. Alan Aldrich, Jessica Harting, John Albers, Greg Strylewicz, Anthony Killeen, Deanna Gabrielson, R. Eastman, Judith Fradkin, Sanford Garfield, Christine Lee, Edward Gregg, Ping Zhang, Dan O’Leary, Gregory Evans, Matthew Budoff, Chris Dailing, Elizabeth Stamm, Ann Schwartz, Caroline Navy, Lisa Palermo, Pentti Rautaharju, Ronald J. Prineas, Elsayed Z. Soliman, Teresa Alexander, Charles Campbell, Sharon Hall, Yabing Li, Margaret Mills, Nancy Pemberton, Farida Rautaharju, Zhuming Zhang, Julie Hu, Susan Hensley, Lisa Keasler, Tonya Taylor, Ronald Danis, Matthew Davis, Larry Hubbard, Barbara Blodi, Ryan Endres, Deborah Elsas, Samantha Johnson, Dawn Myers, Nancy Barrett, Heather Baumhauer, Wendy Benz, Holly Cohn, Ellie Corkery, Kristi Dohm, Amitha Domalpally, Vonnie Gama, Anne Goulding, Andy Ewen, Cynthia Hurtenbach, Daniel Lawrence, Kyle McDaniel, Jeong Pak, James Reimers, Ruth Shaw, Maria Swift, Pamela Vargo, Sheila Watson, Jose A. Luchsinger, Jennifer Manly, Elizabeth Mayer-Davis, Robert R. Moran, Ted Ganiats, Kristin David, Andrew J. Sarkin, Erik Groessl, Naomi Katzir, Helen Chong, William H. Herman, Michael Brändle, Morton B. Brown, Jose C. Florez, David Altshuler, Liana K. Billings, Ling Chen, Maegan Harden, Robert L. Hanson, William C. Knowler, Toni I. Pollin, Alan R. Shuldiner, Kathleen Jablonski, Paul W. Franks, Marie-France Hivert
Journal: Diabetes Care (2022)

To determine whether interventions that slow or prevent the development of type 2 diabetes in those at risk reduce the subsequent prevalence of diabetic retinopathy. The Diabetes Prevention Program (DPP) randomized subjects at risk for developing type 2 diabetes because of overweight/obesity and dysglycemia to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB) to assess the prevention of diabetes. During the DPP and DPP Outcome Study (DPPOS), we performed fundus photography over time on study participants, regardless of their diabetes status. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study grading system, with diabetic retinopathy defined as typical lesions of diabetic retinopathy (microaneurysms, exudates, or hemorrhage, or worse) in either eye. Despite reduced progression to diabetes in the ILS and MET groups compared with PLB, there was no difference in the prevalence of diabetic retinopathy between treatment groups after 1, 5, 11, or 16 years of follow-up. No treatment group differences in retinopathy were found within prespecified subgroups (baseline age, sex, race/ethnicity, baseline BMI). In addition, there was no difference in the prevalence of diabetic retinopathy between those exposed to metformin and those not exposed to metformin, regardless of treatment group assignment. Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia who are at risk for diabetes do not reduce the development of diabetic retinopathy for up to 20 years.